Palladium- and nickel-catalyzed cross-coupling reactions serve as extremely powerful tools in organic chemistry, and they been applied to the total synthesis of a wide array of biologically active targets, including apoptolidin, discodermolide, gambierol, palytoxin, ristocetin aglycone, and taxol. During the upcoming grant period, this program will explore a new dimension of cross-coupling reactions-processes that involve alkyl electrophiles as substrates. Efforts will focus on the development of versatile catalysts, including chiral catalysts, for carbon-carbon bond-forming transformations such as the Suzuki, Negishi, Hiyama, Stille, and Sonogashira reactions. Mechanistic studies will play an important role in this project, since an improved understanding of metal-based reactivity should greatly facilitate catalyst development.